pathogens Review A Summary of the SARS-CoV-2 Vaccines and Technologies Available or under Development Zainalabideen A. Abdulla 1,*, Sharaf M. Al-Bashir 1, Noor S. Al-Salih 2, Ala A. Aldamen 2 and Mohammad Z. Abdulazeez 3 1 Department of Clinical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan; [email protected] 2 Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan; [email protected] (N.S.A.-S.); [email protected] (A.A.A.) 3 Internship Program, Princess Basma Teaching Hospital, Irbid 26125, Jordan; [email protected] * Correspondence: [email protected]; Tel.: +962-2-721-1111 (ext. 7197) Abstract: Since the beginning of 2020, the world has been in a race to develop vaccines that can control the COVID-19 pandemic. More than 250 projects have been initiated for this purpose, but only 14 of them have been authorized for use, despite being in phase 3 clinical trials. More than 40 other vaccines are also in phase 1/2 clinical trials and show promising outcomes. Regarding the appropriate choice of vaccines for each country or region, we reviewed the currently used vaccines in light of the different influencing parameters. These factors include the mode of action, dosage protocol, age group of the vaccinee, side effects, storage conditions, mounted immune response, and cost. Technically, there are seven types of vaccines developed against SARS-CoV-2: messenger RNA (mRNA), nonreplicating and replicating vectors, inactivated viruses, protein subunits, viral-like particles, DNA vaccines, and live attenuated vaccines. The mRNA type is being used for the first Citation: Abdulla, Z.A.; Al-Bashir, S.M.; Al-Salih, N.S.; Aldamen, A.A.; time in humans. Unfortunately, mutated variants of SARS-CoV-2 have started to appear worldwide, Abdulazeez, M.Z. A Summary of the and researchers are investigating the effects of the currently used vaccines on them. There are SARS-CoV-2 Vaccines and many concerns regarding the long-term protection afforded by these vaccines and their side effects, Technologies Available or under and whether they require future modifications to be effective against the mutated variants. The Development. Pathogens 2021, 10, 788. development of new vaccines using more advanced technology is paramount for overcoming the https://doi.org/10.3390/ difficulties in controlling the COVID-19 pandemic across the world. pathogens10070788 Keywords: vaccines; SARS-CoV-2; COVID-19; immune response Academic Editor: Marc Desforges Received: 22 April 2021 Accepted: 18 June 2021 1. Introduction Published: 22 June 2021 Amid the tsunami of the COVID-19 pandemic—with the first known cases reported on Publisher’s Note: MDPI stays neutral 31 December 2019—it was realized that vaccines could play an essential role in increasing with regard to jurisdictional claims in the immunity of the population, preventing severe conditions caused by COVID-19 infec- published maps and institutional affil- tion, reducing the burden on healthcare systems, and minimizing economic losses [1,2]. iations. This crisis prompted an unprecedented race for the development of different vaccines using existing expertise in vaccinology [3]. Traditionally, vaccines require 10–15 years of research, development, and testing before their clinical usage can begin [4]. However, in early 2020, scientists embarked on attempts to produce safe and effective SARS-CoV-2 vaccines at record speed [5]. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. More than 250 vaccine projects were initiated worldwide in 2020, many of which This article is an open access article involve conducting active preclinical trials in animals [6]. According to a recent WHO distributed under the terms and report, 97 vaccines are in clinical trials from phases 1 to 3, and 182 are in their preclinical conditions of the Creative Commons development stages (Figure1)[ 7,8]. Different technologies have been applied in vaccine Attribution (CC BY) license (https:// preparation, some conventional and some newly developed and applied for the first time creativecommons.org/licenses/by/ in humans [8]. Thus far, at least 14 vaccines have reached clinical application and/or have 4.0/). been authorized for use for use against SARS-CoV-2 (Table1). Pathogens 2021, 10, 788. https://doi.org/10.3390/pathogens10070788 https://www.mdpi.com/journal/pathogens Pathogens 2021, 10, 788 2 of 22 Figure 1. The different vaccines in preclinical phases, the three phases of clinical trials, and the authorized vaccines, based on WHO’s recently published numbers [7]. The vaccines against SARS-CoV-2 can be categorized into seven classes (Figure2)[ 9]. The first comprises nucleic acid (RNA or DNA) vaccines; these consist of snippets of the virus’ genetic material, which are injected directly into human body cells. The second class comprises knocked-out virus vaccines, which use inactivated or weakened viruses. The third class is viral vector vaccines, which use Trojan horse nonreplicating vectors—or vectors that replicate much less frequently—to introduce a piece of transcribed DNA from SARS-CoV-2 to another unrelated virus, such as a modified adenovirus. The injected vectors instruct human cells to make coronavirus proteins and trigger an immune response. The fourth class comprises recombinant protein subunit vaccines, which use no genetic material but use whole or fragments of viral proteins packed into nanoparticles for better delivery and uptake by body cells. The fifth class is composed of coronavirus protein subunits; these can be synthesized and assembled to construct virus-like particles (VLPs) similar to those of natural SARS-CoV-2. The sixth class is DNA vaccines that are prepared from viral RNA by reverse transcription. The final class is a group of attenuated and repurposed vaccines based on already-established technology for vaccine preparation (Figure2). Researchers are also evaluating more than 40 vaccines in phase 1/2 clinical trials on humans in various countries; the 43 vaccines that have most progress are listed in Table2. Pathogens 2021, 10, 788 3 of 22 Figure 2. The different seven classes of vaccines against SARS-CoV-2 virus. Table 1. Different leading vaccines currently authorized for use or are in advanced phase 3 clinical trials worldwide. Vaccines Types * Pfizer–BioNTech mRNA [10,11] Moderna mRNA [12] CVnCoV (or CureVac) mRNA [13] Oxford–AstraZeneca Vector-ChAdOx1 [14] Sputnik V by Gamaleya Vector-Ad5 and Ad26 [15] Johnson and Johnson Vector-Ad26 [16] Ad5-nCoV (or Convidecia) Vector-Ad5 [17] Sinopharm Inactivated [18] Sinopharm Wuhan Inactivated [19] CoronaVac Inactivated [20] Covaxin (or BBV 152) by Bharat Biotech Inactivated [21] Novavax COVID-19 Protein subunit [22] EpiVacCorona by Vector Institute Synthetic protein [23] ZF 2001 Protein–RBD dimer [24] * Virus-like particle (VLP) vaccines are not approved for usage yet. Pathogens 2021, 10, 788 4 of 22 Table 2. Vaccines of different categories against SARS-CoV-2 virus in phase 1/2 clinical trials. Vaccines Types ARCoV by China’s PLA Academy of Military Science (AMS), Suzhou Abogen Biosciences, and mRNA [25] Walvax Biotechnology Chulalongkorn University (Thailand) mRNA [26] LUNAR-COVID 19 by Arcturus Therapeutics and mRNA “self-amplifying” [27] Duke-NUS Medical School HGCO19 by Gennova Bio India and HDT Bio Seattle mRNA “self-amplifying” [28] VacEquity Global Health (Imperial College, U.K.) Self amplifying RNA, skin implanted [29,30] Covigenix VAX-001 by Entos Pharmaceuticals DNA, nucleocapsid gene [31] (Canada) DNA bacTRL-Spike by Symvivo (Canada) DNA in a bacterial vector, oral [32] CORVax 12 DNA for S protein and pIL-12 [33] AG0302 by Japanese AnGes, Osaka University, and DNA, skin injection [34] Takara Bio Zydus Cadila (India) DNA, skin patch [35] INO-4800 by Inovio (Pennsylvania-based company) DNA injection by skin device [36] GeneOne Life Science (South Korea-based biotech DNA encoding two proteins [37] company) COVID-eVax DNA fragment [38] GRAd-COV2 by ReiThera (Italy) with Leukocare Simian Ad GRAd vectored [39] (Germany) and Univercells (Belgium) Vaxart (USA) Ad5-vectored, oral [40] AdCOVID by Altimmune Company Ad5-vectored, nasal [41,42] Convidecia (or Ad5-nCoV) Ad5-vectored [43] AdCLD-CoV19 by Cellid and IVI Biotech Co. Ad5- and Ad35-vectored [44,45] Flu-Covid Nasal by University of Hong Kong and Influenza virus-vectored [46] Xiamen University MVA-SARS-2-S by DZIF and IDT Biologika MVA orthopoxvirus-vectored [47] BriLife by Israel Institute for Biological Research Vesicular stomatitis virus-vectored [48] Recombinant vaccine by West China Hospital and RBD of S protein in insect cells [49] Sichuan University Adimmune (Taiwan-based manufacturer) RBD of S protein [50] Shionogi (Japanese pharmaceutical company) Protein in insect cells [51] Soberana 02 by Finlay Institute of Vaccines (Cuba) RBD with tetanus toxoid [52] CoVLP by Medicago and GSK (Canada) Virus like-particles in plant cells [53] Kentucky BioProcessing Protein in plant cells (NBR) [54] Dynavax by Clover Pharmaceuticals (China) S-Trimer protein [55] COVAXX (New York, USA) Multitope peptide-based [56] University of Tübingen (Germany) Eight parts of two viral proteins [57] COVAX 19 of Vaxine (Australia) Protein subunit [58] SpyBiotech and Serum Institute of India Coronavirus RBD and HBsAg VLPs [59] Mambisa by Center for Genetic Engineering and RBD and HBV nasal spray [60] Biotechnology (Cuba) Abdala by Center of Genetic Engineering and RBD of S protein [61] Biotechnology (Cuba) SK Bioscience (South Korea) S protein [62] Nanocovax by Nanogen Pharmaceuticals (Vietnam) Protein-based [63,64] COVAC by University of Saskatchewan (Canada) Protein subunits [65] CoviVac by Chumakov Centre (Russia) Inactivated [66] Valneva (France-based company) Inactivated [67] ERUCOV-VAC by Erciyes University (Turkey) Inactivated [68] QazCovid-in by RIBSP (Kazakhstan) Inactivated [69] COVIran Barekat by Shifa Pharmed (Iran) Inactivated [70] COVI-VAC (intranasal) by Codagenix Live attenuated, nasal [71] 2. The Viral Spike (S) Protein The S protein is frequently considered the major antigen target for vaccines against the SARS-CoV-2 virus.